The effects of forced exercise and zinc supplementation during pregnancy on prenatally stress-induced behavioral and neurobiological consequences in adolescent female rat offspring.

Prenatal manipulations can lead to neurobehavioral changes in the offspring. In this study, individual and combined effects of forced exercise and zinc supplementation during pregnancy on prenatally restraint stress (PRS)-induced behavioral impairments, neuro-inflammatory responses, and oxidative stress have been investigated in adolescent female rat offspring. Pregnant rats were divided into five groups: control; restraint stress (RS); RS + exercise stress (RS + ES), RS + zinc supplementation (RS + Zn); and RS + ES + Zn. All the pregnant rats (except control) were exposed to RS from gestational days 15 to 19. Pregnant rats in ES groups were subjected to forced treadmill exercise (30 min/daily), and in Zn groups to zinc sulfate (30 mg/kg/orally), throughout the pregnancy. At postnatal days 25-27, anxiety-like and stress-coping behaviors were recorded, and the gene expressions of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) and the concentration of total antioxidant capacity were measured in the prefrontal cortex. PRS significantly enhanced anxiety, generated passive coping behaviors, increased IL-1ß and TNF-α expression, and decreased the antioxidant capacity. ES potentiated while zinc reversed PRS-induced behavioral impairments. Prenatal zinc also restored the anti-inflammatory and antioxidant capacity but had no effect on additive responses imposed by the combination of RS and ES. Suppression of PRS-induced behavioral and neurobiological impairments by zinc suggests the probable clinical importance of zinc on PRS-induced changes on child temperament.

Protective effects of forced exercise against topiramate-induced cognition impairment and enhancement of its antiepileptic activity: molecular and behavioral evidences.

Propose/aim of study: Forced exercise can act as a neuroprotective factor and cognitive enhancer. The aim of the current study was to evaluate the effects of forced exercise on topiramate (TPM) induced cognitive impairment and also on TPM anti-seizure activity and neurodegeneration status after seizure.Material and method: Forty adult male rats were divided into four groups receiving normal saline, TPM (100 mg/kg), TPM in combination with forced exercise and forced exercise only respectively for 21 days. MWM test, and PTZ induced seizure were used and some oxidative, inflammatory and apoptotic biomarkers were measured for assessment of experimental animals.Results: Forced exercise in combination with TPM could abolish the TPM induced cognitive impairment and potentiates its anti-seizure activity. Also forced exercise in combination with TPM decreased malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1ß) and Bax protein, while caused increase in superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities after PTZ administration.Conclusion: It seems that forced exercise could act as an adjunct therapy with TPM for management of induced cognitive impairment and can also potentiate TPM antiepileptic and neuroprotective effects.

Comparison of murine behavioural and physiological responses after forced exercise by electrical shock versus manual prodding.

NEW FINDINGS: What is the central question of this study? Forced treadmill exercise using electrical shock is the most common technique in rodent exercise studies. Here, we examined how the use of electrical shock during forced treadmill exercise affects behavioural and physiological responses in comparison to a novel non-electrical shock technique. What is the main finding and its importance? In comparison to mice that underwent traditional treadmill running induced by electrical shock, mice that underwent forced running using a novel technique involving gentle prodding to induce running showed: (i) higher locomotor activity; (ii) less anxiety-like behaviour; and (iii) altered exercise-induced muscle pain immediately after exercise. ABSTRACT: Animal models of exercise have been useful to understand underlying cellular and molecular mechanisms. Many studies have used methods of exercise that are unduly stressful (e.g., electrical shock to force running), potentially skewing results. Here, we compared physiological and behavioural responses of mice after exercise induced using a prodding technique that avoids electrical shock versus a traditional protocol using electrical shock. We found that exercise performance was similar for both techniques; however, the shock group demonstrated significantly lower locomotor activity and higher anxiety-like behaviour. We also observed divergent effects on muscle pain; the prodding group showed hyperalgesia immediately after exercise, whereas the shock group showed hypoalgesia. Corticosterone concentrations were elevated to a similar extent for both groups. In conclusion, mice that were exercised without shock generated similar maximal exercise performance, but postexercise these mice showed an increase in locomotor activity, less anxiety-like behaviour and altered muscle pain in comparison to mice that exercised with shock. Our data suggest that running of mice without the use of electrical shock is potentially less stressful and might be a better technique to study the physiological and behavioural responses to exercise.

Impact of different intensities of forced exercise on deficits of spatial and aversive memory, anxiety-like behavior, and hippocampal BDNF during morphine abstinence period in male rats.

Forced exercise can alleviate cognitive-behavioral deficits in an experimental model of addiction. However, the effects of different intensities of forced exercise in improving behavioral, cognitive and biochemical deficits during morphine abstinence period are not well investigated. Thus, the current work examined the effects of different loads of forced exercise on cognition functions, anxiety behavior and BDNF changes in the hippocampus, and prefrontal cortex (PFC), and also serum levels of BDNF and corticosterone during the abstinent period in male rats. Animals received morphine injections (10 mg/kg, twice a day) for 10 consecutive days. Then, the animals were exposed to a 4-week forced exercise training program under low, moderate or high intensities (30 min per session on 5 days a week), which accompanied by behavioral and biochemical tests. In Experiment 1, anxiety-like behaviors using elevated plus maze (EPM), and light/dark box (L/D box) were examined. In Experiment 2, cognitive functions using T-maze alteration and passive avoidance tasks were tested, which accompanied by BDNF measurements in the hippocampus and PFC. In Experiment 3, serum levels of BDNF and corticosterone following the termination of forced exercise regimen were measured. Morphine-abstinent animals exhibited anxiogenic -like behaviors in the EPM, but not L/D box. They also exhibited impaired T-maze alternation performance and passive avoidance memory, and a decline in hippocampal BDNF, but not PFC. Forced exercise at a moderate intensity alleviated anxiety, cognitive and BDNF defects in morphine-abstinent animals. The high load exercise enhanced serum levels of corticosterone in both saline and morphine groups. Thus, regular moderate forced exercise may be beneficial in preserving cognitive and mood functions in male addicts during the abstinent period and drug rehabilitation.

Combining restricted diet with forced or voluntary exercises improves hippocampal BDNF and cognitive function in rats.

Dietary restriction (RDt) and exercise (Ex) enhances cognitive function due, at least in part, levels of neurotrophins such as brain-derived neurotrophic factor (BDNF). This study examined changes in BDNF levels and data acquisition and retention following every-other-day RDt alone, and combined with either voluntary wheel (VxRDt) or forced swimming Exs (FxRDt) in rats. Hippocampal BDNF was measured using ELISA while learning and memory formation were assessed with the radial arm water maze (RAWM) paradigm. After 6 weeks, VxRDt and FxRDt enhanced BDNF levels, and short- and long-term memories (p < 0.05). The magnitude of the increase in BDNF was significantly higher in VxRDt group than in other groups (p < 0.05). However, no differences were found in learning and memory formation between the Ex regiments (VxRDt versus FxRDt). Additionally, RDt alone neither modulated BDNF level nor enhanced learning and memory formation (p > 0.05). These results suggest more important role of Ex, as opposed to RDt, in enhancing learning and memory formation. In addition, VxRDt appears to be more potent in enhancing brain BDNF levels than FxRDt, when combined with RDt in rats.

Design and Development of a Smart Exercise Bike for Motor Rehabilitation in Individuals with Parkinson's Disease.

Recent studies in rehabilitation of Parkinson's disease (PD) have shown that cycling on a tandem bike at a high pedaling rate can reduce the symptoms of the disease. In this research, a smart motorized bicycle has been designed and built for assisting Parkinson's patients with exercise to improve motor function. The exercise bike can accurately control the rider's experience at an accelerated pedaling rate while capturing real-time test data. Here, the design and development of the electronics and hardware as well as the software and control algorithms are presented. Two control algorithms have been developed for the bike; one that implements an inertia load (static mode) and one that implements a speed reference (dynamic mode). In static mode the bike operates as a regular exercise bike with programmable resistance (load) that captures and records the required signals such as heart rate, cadence and power. In dynamic mode the bike operates at a user-selected speed (cadence) with programmable variability in speed that has been shown to be essential to achieving the desired motor performance benefits for PD patients. In addition, the flexible and extensible design of the bike permits readily changing the control algorithm and incorporating additional I/O as needed to provide a wide range of riding experiences. Furthermore, the network-enabled controller provides remote access to bike data during a riding session.

Regular treadmill exercise prevents sleep deprivation-induced disruption of synaptic plasticity and associated signaling cascade in the dentate gyrus.

STUDY OBJECTIVES: Evidence suggests that regular exercise can protect against learning and memory impairment in the presence of insults such as sleep deprivation. The dentate gyrus (DG) area of the hippocampus is a key staging area for learning and memory processes and is particularly sensitive to sleep deprivation. The purpose of this study was to determine the effect of regular exercise on early-phase long-term potentiation (E-LTP) and its signaling cascade in the presence of sleep deprivation. EXPERIMENTAL DESIGN: Rats were exposed to 4 weeks of regular treadmill exercise then subsequently sleep-deprived for 24h using the modified multiple platform model before experimentation. We tested the effects of exercise and/or sleep deprivation using electrophysiological recording in the DG to measure synaptic plasticity; and Western blot analysis to quantify the levels of key signaling proteins related to E-LTP. MEASUREMENTS AND RESULTS: Regular exercise prevented the sleep deprivation-induced impairment of E-LTP in the DG area as well as the sleep deprivation-associated decrease in basal protein levels of phosphorylated and total α calcium/calmodulin-dependent protein kinase II (P/total-CaMKII) and brain-derived neurotrophic factor (BDNF). High frequency stimulation (HFS) to the DG area was used to model learning stimuli and increased the P-CaMKII and BDNF levels in normal animals: yet failed to change these levels in sleep-deprived rats. However, HFS in control and sleep-deprived rats increased the levels of the phosphatase calcineurin. In contrast, exercise increased BDNF and P-CaMKII levels in exercised/sleep-deprived rats. CONCLUSIONS: Regular exercise appears to exert a protective effect against sleep deprivation-induced spatial memory impairment by inducing hippocampal signaling cascades that positively modulate basal and stimulated levels of key effectors such as P-CaMKII and BDNF, while attenuating increases in the protein phosphatase calcineurin.

Changes in calpains and calpastatin in the soleus muscle of Daurian ground squirrels during hibernation.

We investigated changes in muscle mass, calpains, calpastatin and Z-disk ultrastructure in the soleus muscle (SOL) of Daurian ground squirrels (Spermophilus dauricus) after hibernation or hindlimb suspension to determine possible mechanisms by which muscle atrophy is prevented in hibernators. Squirrels (n=30) were divided into five groups: no hibernation group (PRE, n=6); hindlimb suspension group (HLS, n=6); two month hibernation group (HIB, n=6); two day group after 90±12 days of hibernation (POST, n=6); and forced exercise group (one time forced, moderate-intensity treadmill exercise) after arousal (FE, n=6). Activity and protein expression of calpains were determined by casein zymography and western blotting, and Z-disk ultrastructure was observed by transmission electron microscopy. The following results were found. Lower body mass and higher SOL muscle mass (mg) to total body mass (g) ratio were observed in HIB and POST; calpain-1 activity increased significantly by 176% (P=0.034) in HLS compared to the PRE group; no significant changes were observed in calpain-2 activity. Protein expression of calpain-1 and calpain-2 increased by 83% (P=0.041) and 208% (P=0.029) in HLS compared to the PRE group, respectively; calpastatin expression increased significantly by 180% (P<0.001) and 153% (P=0.007) in HIB and POST, respectively; the myofilaments were well-organized, and the width of the sarcomere and the Z-disk both appeared visually similar among the pre-hibernation, hibernating and post-hibernation animals. Inhibition of calpain activity and consequently calpain-mediated protein degradation by highly elevated calpastatin protein expression levels may be an important mechanism for preventing muscle protein loss during hibernation and ensuring that Z-lines remained ultrastructurally intact.

The different cell-specific mechanisms of voluntary exercise and forced exercise in the nucleus accumbens.

Physical inactivity is a global epidemic. People who take the initiative to exercise will feel pleasure during the exercise process and stick with it for a long time, while people who passively ask for exercise will feel pain and cannot stick with it. However, the neural mechanisms underlying voluntary and forced exercise remain unclear. Here, we report that voluntary running increased the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSC) but decreased membrane excitability in D1R-MSNs, whereas D2R-MSNs did not change in mEPSC and membrane excitability. Forced running increased the frequency of mEPSC and membrane excitability in D2R-MSNs, but D1R-MSNs did not change, which may be the mechanism by which forced exercise has a non-rewarding effect. These findings provide new insights into how voluntary and forced exercise mediate reward and non-reward effects.

The effect of exercise on early sensorimotor performance alterations in the 3xTg-AD model of Alzheimer's disease.

Alzheimer's disease (AD) is characterized by a progressive decline in cognitive function; however, recent evidence suggests that non-cognitive sensorimotor and psychomotor symptoms accompany early stages of the disease in humans and AD models. Although exercise is emerging as an important therapeutic to combat AD progression, little is known about the effect of exercise on sensorimotor domain functions. The purpose of this study was to determine if early sensorimotor symptoms accompany deficits in Morris water maze (MWM) performance in the 3xTg-AD model, and investigate if exercise could protect against early behavioral decline. 3xTg-AD and wild-type (WT) control mice were subjected to 12 weeks of moderate intensity wheel running or remained sedentary. At 6 months of age, animals underwent a series of sensorimotor and MWM testing. 3xTg-AD mice displayed deficits in sensorimotor function (beam traversal, spontaneous activity, and adhesive removal) and MWM performance. Interestingly, 3xTg-AD animals exhibited increased freezing and unusual shaking/tremoring behaviors not displayed by WT controls. Exercise improved beam traversal, adhesive removal, and reduced the unusual motor-related behaviors in 3xTg-AD mice. Our study shows that sensorimotor symptoms coincide with deficits in MWM performance, and suggest that exercise may mitigate deficits associated with early disease in 3xTg-AD mice.

Differential effects of voluntary and forced exercise trainings on spatial learning ability and hippocampal biomarkers in aged female rats.

This study aimed to compare the effects of voluntary and forced exercise trainings on cognitive functions and to evaluate their relationship with hippocampal synaptic proteins, neurotrophic factors and markers of oxidative damage in aged female rats. Aged female rats were randomly assigned to control, voluntary exercise training and forced exercise training groups. Voluntary or forced exercise trainings were performed for 12 weeks. At the end of the training period, cognitive functions of the animals were assessed with Morris water maze (MWM) test. After the behavioral test, hippocampus tissues were taken for the analysis of synaptophysin, acetylcholinesterase (AChE), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), malondialdehyde (MDA), protein carbonyl (PC), glutathione (GSH) and superoxide dismutase (SOD). During the MWM test, the number of platform crossings was higher in the voluntary exercise group than in the control group (P < 0.05). In the hippocampus tissue, levels of the synaptophysin, BDNF, NGF and SOD were higher, but MDA levels were lower in the voluntary exercise group than in the control group (P < 0.05). Additionally, hippocampal AChE concentration was higher, but PC levels were lower in the both voluntary and forced exercise groups than in the control group (P < 0.05). In conclusion, voluntary exercise was more effective intervention to improve spatial learning ability in aging process. Increased neurotrophic factors, synaptic proteins, and improved oxidative damage may play a role in these positive effects.

Effects of different intensities of treadmill exercise on cued fear extinction failure, hippocampal BDNF decline, and Bax/Bcl-2 ratio alteration in chronic-morphine treated male rats.

Chronic morphine impairs cued fear extinction, which may contribute to the high prevalence of anxiety disorders and the replase of opiate addiction. This work investigated the effects of forced exercise with different intensities on cued fear extinction impairment and alternations of hippocampal BDNF and apoptotic proteins induced by chronic morphine. Rats were injected with bi-daily doses of morphine or saline for ten days and then received a cued or contextual fear conditioning training, which was followed by fear extinction training for four consecutive days. Cued, but the not contextual fear response was impaired in morphine-treated rats. Then, different saline or morphine-treated rats underwent forced exercise for 4-weeks with light, moderate or high intensities. Subsequently, rats received a cued fear conditioning followed by four days of extinction training, and the expression of hippocampal BDNF and apoptotic proteins was determined. A relatively long time after the last injection of morphine (35 days), rats again showed cued fear extinction failure and reduced hippocampal BDNF, which recovered by light and moderate, but not high exercise. Light and moderate, but not high-intensity treadmill exercise enhanced the up-regulation of Bcl-2 and down-regulation of the Bax proteins in both saline- and morphine-treated rats, which shifted the balance between pro-apoptotic and anti-apoptotic factors in favor of cell survival. These findings highlight the impact of exercise up to moderate intensity in the recovery of cued extinction failure, more likely via BDNF in addicted individuals.

A Handful of Details to Ensure the Experimental Reproducibility on the FORCED Running Wheel in Rodents: A Systematic Review.

A well-documented method and experimental design are essential to ensure the reproducibility and reliability in animal research. Experimental studies using exercise programs in animal models have experienced an exponential increase in the last decades. Complete reporting of forced wheel and treadmill exercise protocols would help to ensure the reproducibility of training programs. However, forced exercise programs are characterized by a poorly detailed methodology. Also, current guidelines do not cover the minimum data that must be included in published works to reproduce training programs. For this reason, we have carried out a systematic review to determine the reproducibility of training programs and experimental designs of published research in rodents using a forced wheel system. Having determined that most of the studies were not detailed enough to be reproducible, we have suggested guidelines for animal research using FORCED exercise wheels, which could also be applicable to any form of forced exercise.

Interactive Effects of Enalapril Administration and Novel HIIT Wheel-Bed Training in Aged Rats.

INTRODUCTION: Growing research suggests that aerobic high-intensity interval training (HIIT) improves cardiovascular function and physical performance compared with moderate intensity continuous training (MICT). However relatively few animal models of HIIT are available to inform about the benefits of this exercise-particularly among older animals. In addition, there is little evidence for how HIIT training interacts with adjuvant pharmacological therapies known to enhance the impact of MCIT in older individuals such as Angiotensin Converting Enzyme (ACE) Inhibitors. PURPOSE: The aim of the present study was to establish a HIIT protocol in aged rats based on forced running wheel-bed, and to subsequently (1) establish the feasibility of the HIIT protocol in a proof-of-concept study evaluating interactions between HIIT and (2) the result of combining HIIT + ACE inhibitor treatment using the ACE inhibitor enalapril. METHODS: Two groups of rats were used in this study. The feasibility of using wheel-bed for HIIT training was tested in group one (15- and 30-month-old male rats). In the second group, 37 24-month-old Fisher 344 × Brown Norway male rats were randomly divided into four subgroups: control, enalapril, HIIT training group, and HIIT training combined with enalapril administration. The training and administration lasted for 4 weeks. After the intervention, locomotor activity, exercise tolerance, and grip strength were tested. RESULTS: Our feasibility study suggested that middle-aged and aged rats were able to successfully complete the HIIT training. In our intervention study, HIIT training alone, regardless of adjuvant enalapril intervention, did raise treadmill exercise tolerance vs. the sedentary condition. Measures of healthspan were not negatively impacted by HIIT training. CONCLUSION: The novel HIIT protocol based on forced running wheel-bed was successfully employed in aged rats. We conclude that future studies should compare the results and of multi-modal intervention strategies which include both HIIT and MICT in combination with adjuvant therapies such as enalapril to improve exercise tolerance and other global indices of healthspan.

Difference in the brain serotonin and its metabolite level and anxiety-like behavior between forced and voluntary exercise conditions in rats.

Physical exercise is beneficial to both physical and mental health, though it is unclear whether voluntary and forced exercise have the same effects. We investigated the effects of chronic forced and voluntary wheel running on brain levels of serotonin (5-HT), its metabolite 5-hydroxyindoleacetic acid (5-HIAA), and anxiety-like behavioral change in rats. Forty-eight rats were randomly assigned to standard cages (sedentary control: SC); voluntary exercise (free running on a wheel, V-EX); voluntary limited exercise (wheel available only 1 h per day, VL-EX); and forced exercise (running on a motorized wheel, F-EX). After 4 weeks, rats either underwent the open field test (OFT) or their 5-HT and 5-HIAA levels were measured in the major serotonergic neural cell bodies and projection areas. 5-HT and 5-HIAA levels in the dorsal and median raphe nuclei were increased in the V-EX, but not in the VL-EX and F-EX groups, compared with the SC group. In the paraventricular hypothalamic nucleus and caudate putamen, only 5-HT levels were increased in the V-EX group. Interestingly, in the amygdala, only 5-HIAA levels were significantly increased in the V-EX group. Conversely, we found that F-EX rats showed no significant 5-HT changes and increased anxiety-like behavior. VL-EX did not have significant beneficial effects on any of the experimental parameters. These data suggest that only unlimited voluntary exercise stimulates the serotonergic system and suppresses anxiety-like behavior.

Therapeutic effects of forced exercise cycling in individuals with Parkinson's disease.

Currently there is no cure for the progressive movement disorders associated with Parkinson's Disease (PD). Pharmacological management of movement disorders in PD are associated with significant negative side effects. Exercise improves the efficacy of anti-parkinsonian medication, but does not ameliorate the side effects. Consensus on the optimal mode of exercise training or dosing to improve motor function for individuals with PD is lacking. The new concept of forced exercise is gaining traction in the literature as a mode of exercise which has the potential to improve motor function in individuals with PD. The purpose of this article is to review the effects of forced exercise on specific components of motor function that would help guide clinical decision making and exercise prescription for the PD patient population. Collectively, the evidence provided in this review suggests that forced exercise may be safely added as an ancillary therapy to the medical management of PD.

Beneficial effects of voluntary over forced exercise on skeletal muscle structure and myokines' expression.

BACKGROUND: Myokines, a group of small proteins - mainly cytokines, are released by myocytes during muscular contraction and proved to have many biological effects locally or at systemic levels. The main objective was to study the morphological alterations and myokines expression in rat gastrocnemius muscle following forced compared to voluntary muscle contraction. MATERIALS AND METHODS: Thirty-six adult male Wistar rats were divided into three groups: control, voluntary exercise and forced swimming regimen. The experiment last for 3 weeks. The weight of rats and serum corticosterone levels were recorded. The gastrocnemius muscle samples were processed for histological and immunohistochemical study of different myokines. RESULTS: The mean weight of rats showed no statistical difference between groups. Corticosterone level significantly increased after forced exercise. Voluntary exercise muscle fibres appeared hypertrophied with prominent transverse banding and dominating satellite cells. Forced exercise muscle showed atrophied widely spaced muscle fibres and inflammatory cell infiltrate. Voluntary exercise significantly increased optic density of interleukin 6, macrophage inhibitory and brain derived neurotrophic factors, whereas the forced exercise group showed significant decrease in their optic densities. The optic density of vascular endothelial growth factor significantly decreased in the forced exercise group. Forced exercise could be harmful to the skeletal muscle fibres and it decreases the secretion of important myokines. Further, forced exercise significantly increases the serum corticosterone level. CONCLUSIONS: The use of exercise for the attainment of healthy life style or in psycho- or neuro-therapy should follow a thoroughly studied programme for welfare of human health.

Forced, Not Voluntary, Aerobic Exercise Enhances Motor Recovery in Persons With Chronic Stroke.

Background. The recovery of motor function following stroke is largely dependent on motor learning-related neuroplasticity. It has been hypothesized that intensive aerobic exercise (AE) training as an antecedent to motor task practice may prime the central nervous system to optimize motor recovery poststroke. Objective. The objective of this study was to determine the differential effects of forced or voluntary AE combined with upper-extremity repetitive task practice (RTP) on the recovery of motor function in adults with stroke. Methods. A combined analysis of 2 preliminary randomized clinical trials was conducted in which participants (n = 40) were randomized into 1 of 3 groups: (1) forced exercise and RTP (FE+RTP), (2) voluntary exercise and RTP (VE+RTP), or (3) time-matched stroke-related education and RTP (Edu+RTP). Participants completed 24 training sessions over 8 weeks. Results. A significant interaction effect was found indicating that improvements in the Fugl-Meyer Assessment (FMA) were greatest for the FE+RTP group (P = .001). All 3 groups improved significantly on the FMA by a mean of 11, 6, and 9 points for the FE+RTP, VE+RTP, and Edu+RTP groups, respectively. No evidence of a treatment-by-time interaction was observed for Wolf Motor Function Test outcomes; however, those in the FE+RTP group did exhibit significant improvement on the total, gross motor, and fine-motor performance times (P ≤ .01 for all observations). Conclusions. Results indicate that FE administered prior to RTP enhanced motor skill acquisition greater than VE or stroke-related education. AE, FE in particular, should be considered as an effective antecedent to enhance motor recovery poststroke.

Functional and Brain Activation Changes Following Specialized Upper-Limb Exercise in Parkinson's Disease.

For the management of Parkinson's disease (PD), the concept of forced exercise (FE) has drawn interest. In PD subjects, the FE executed with lower limbs has been shown to lessen symptoms and to promote brain adaptive changes. Our study is aimed to investigate the effect of an upper-limb exercise, conceptually comparable with the FE, in PD. Upper-limb exercise was achieved in a sitting position by using a specially designed device (Angel's Wings®). Clinical data, computerized dynamic posturography, magnetic resonance imaging (MRI) (resting-state MRI and arterial spin labeling), and neuropsychological tests were used before and after 2 months' exercise training. We found a significant long-lasting improvement in Unified Parkinson Disease Rating Scale (UPDRS)-III and cognitive scales, along with improvement in balance and postural control (better alignment of the gravity center and improvement in weight symmetry and in anticipatory motor strategies). Computerized dynamic posturography pointed out an enhanced central ability to integrate the vestibular signals with afferents from other sensory systems. Neuroimaging analyses after 2 months' exercise training showed, with respect to pretraining condition, many changes. An increase of the cerebral blood flow was evident in the left primary motor cortex (M1), left supplementary motor cortical area, and left cerebellar cortex. The bilateral globus pallidus showed an increased functional connectivity to the right central operculum, right posterior cingulate gyrus, and left sensorimotor cortex. Seed-to-voxel analysis demonstrated a functional connectivity between M1 and the left superior frontal gyrus. Left crus II showed strengthened connections with the left pre-rolandic area, left post-rolandic area, and left supramarginal area. These findings likely reflect compensatory mechanisms to the neuropathological hallmark of PD. Overall, our results show that this upper-limb exercise model, conceptually comparable with the FE already tested in the lower limbs, leads to a global improvement (involving non-exercised limbs) likely consistent with the functional changes observed in the central nervous system.

Voluntary, involuntary and forced exercises almost equally reverse behavioral impairment by regulating hippocampal neurotrophic factors and oxidative stress in experimental Alzheimer's disease model.

The purpose of this study was to compare the neuroprotective effects of voluntary, involuntary, and forced exercise trainings on behavioral impairment as well as hippocampal Alzheimer's disease (AD) pathology and oxidative stress markers, and levels of neurotrophic factors in the rat model of AD. The rats were assigned to control, Alzheimer model, Alzheimer + voluntary exercise, Alzheimer + involuntary exercise, or Alzheimer + forced exercise group. The rat model of AD was established by D-(+)-Galactose (D-GAL) and AlCl3 administration for 90 days. Voluntary, involuntary (swimming) or forced exercise (load-swimming) trainings were performed for 90 days starting with the D-GAL and AlCl3 administration and then several behavioral tests were applied. Locomotor activity, exploratory behavior, and spatial memory were lower but anxiety levels were higher in the Alzheimer model group, than in the other groups (P < 0.05). The hippocampal levels of the amyloid beta 1-42, microtubule associated protein Tau, malondialdehyde, and protein carbonyl levels were higher, but brain-derived neurotrophic factor, nerve growth factor, glutathione and superoxide dismutase levels were lower in the Alzheimer model group, than in the other groups (P < 0.05). The results of the present study suggest that all exercise modalities almost equally attenuated non-cognitive and cognitive disturbances in a rat model of AD. Elevated neurotrophic factors, and improved oxidative stress could mediate these beneficial effects.